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31. 发明授权

US06350729B1 Inhibition of nitric oxide-mediated hypotension and septic shock with iron-containing hemoprotein 失效
标题翻译：用含铁血红蛋白抑制一氧化氮介导的低血压和败血性休克
公开(公告)号：US06350729B1
公开(公告)日：2002-02-26
申请号：US09615353
申请日：2000-07-13
申请人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
发明人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
IPC分类号： A61K3842
CPC分类号： A61K38/42 , Y02A50/411
摘要： The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also directed to a method for the treatment of septic shock.
摘要翻译：本发明涉及一种用于预防或治疗由生物反应调节剂引起的一氧化氮产生引起的全身性低血压的有害生理作用的动物的方法。这种生物反应调节剂的实例包括但不限于细胞因子和内毒素。本发明还涉及一种治疗败血性休克的方法。

32. 发明授权

US06172039B2 Expression of recombinant hemoglobin and hemoglobin variants in yeast 失效
标题翻译：酵母中重组血红蛋白和血红蛋白变体的表达
公开(公告)号：US06172039B2
公开(公告)日：2001-01-09
申请号：US08463160
申请日：1995-06-05
申请人： Joseph De Angelo , Nalini M. Motwani , Wajeeh Bajwa , Joseph Bonaventura
发明人： Joseph De Angelo , Nalini M. Motwani , Wajeeh Bajwa , Joseph Bonaventura
IPC分类号： C07K14805
CPC分类号： C12N15/81 , A61K38/00 , C07K14/805 , Y02A50/473
摘要： The invention is directed to a substantially pure mammalian globin chain or heme-binding fragment thereof. The invention is further directed to recombinant DNA vectors capable of expressing at least one globin chain or substantially homologous variant thereof in yeast. The invention also relates to methods for expressing at least one globin chain or substantially homologous variant thereof in yeast. Expressed alpha-like globin and beta-like globin chains or variants thereof may be combined with a source of heme to produce hemoglobin or a substantially homologous variant thereof. Additionally, expressed gamma-globin chains may be combined with a source of heme to produce hemoglobin or a substantially homologous variant thereof. The invention also relates to methods for expressing hemoglobin or variants thereof in yeast where the heme is produced by the yeast and ligated to globins to form hemoglobin in vivo. The hemoglobin produced by the methods of the present invention may be used in applications requiring a physiological oxygen carrier such as in blood substitute solutions and as in plasma expanders or in applications requiring a physiological oxygen carrier.
摘要翻译：本发明涉及基本上纯的哺乳动物球蛋白链或其血红素结合片段。本发明还涉及能够在酵母中表达至少一种珠蛋白链或基本上同源的变体的重组DNA载体。本发明还涉及用于在酵母中表达至少一种珠蛋白链或基本上同源的变体的方法。表达的α样球蛋白和β样球蛋白链或其变体可以与血红素来源组合以产生血红蛋白或其基本上同源的变体。此外，表达的γ-珠蛋白链可以与血红素来源组合以产生血红蛋白或其基本上同源的变体。本发明还涉及在酵母中表达血红蛋白或其变体的方法，其中血红素由酵母产生并与球蛋白结合以在体内形成血红蛋白。通过本发明的方法产生的血红蛋白可以用于需要生理氧载体的应用中，例如在血液替代溶液中，以及在等离子体扩张器中或在需要生理氧载体的应用中。

33. 发明授权

US6153186A Red blood cells loaded with S-nitrosothiol and uses therefor 失效
标题翻译：装有S-亚硝基硫醇的红细胞并用于此
公开(公告)号：US6153186A
公开(公告)日：2000-11-28
申请号：US616255
申请日：1996-03-15
申请人： Jonathan S. Stamler , Joseph Bonaventura
发明人： Jonathan S. Stamler , Joseph Bonaventura
IPC分类号： A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K31/198 , A61K35/18 , A61K38/00 , A61K38/42 , A61K47/48 , A61P5/30 , A61P5/42 , A61P7/00 , A61P7/06 , A61P11/00 , C07K14/00 , C12N5/08 , G01N21/63 , G01N21/76 , G01N33/72 , C12N5/06
CPC分类号： A61K33/00 , A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K35/18 , A61K47/48023 , A61K47/48307 , A61K47/48776 , C07K14/00 , G01N21/631 , G01N21/76 , G01N33/721
摘要： Nitric oxide (NO) interacts with hemoglobin (Hb) at its metal centers, whereas S-nitrosothiols (RSNOs) can donate the NO group to .beta.93 cysteine residues, thereby shielding the NO functionality from heme inactivation. S-nitrosylation of Hb is under the allosteric control of oxygen and the oxidation state of heme. NO group release from SNO-Hb is further facilitated by intracellular low molecular weight thiols, forming RSNOs which can be exported from the erythrocyte to regulate blood pressure. Red blood cells can be loaded with low molecular weight RSNOs to act as a delivery system for NO.sup.+ groups. Loaded red blood cells can be used in methods of therapy for conditions which are characterized by abnormal O.sub.2 metabolism of tissues, oxygen-related toxicity, abnormal vascular tone, abnormal red blood cell adhesion, or abnormal O.sub.2 delivery by red blood cells.
摘要翻译：一氧化氮（NO）在其金属中心与血红蛋白（Hb）相互作用，而S-亚硝基硫醇（RSNO）可以将NO基团提供给β93半胱氨酸残基，从而屏蔽NO功能不受血红素灭活。 Hb的S-亚硝基化在氧的变构控制下以及血红素的氧化态。通过细胞内低分子量硫醇进一步促进SNO-Hb的NO释放，形成可从红细胞输出以调节血压的RSNO。红细胞可以装载低分子量的RSNO作为NO +组的递送系统。加载的红细胞可用于以组织异常氧代谢，氧相关毒性，异常血管紧张，红细胞异常粘附或红细胞异常氧传递为特征的病症的治疗方法。

34. 发明授权

US5900403A Use of iron hemoprotein for treating pathogenic syndrome caused by nitric oxide overproduction 失效
标题翻译：使用铁血蛋白治疗由一氧化氮过量产生引起的致病综合征
公开(公告)号：US5900403A
公开(公告)日：1999-05-04
申请号：US942632
申请日：1997-10-02
申请人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
发明人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
IPC分类号： A61K38/16 , A61K38/42 , A61P9/00 , A61P9/12
CPC分类号： A61K38/42
摘要： The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also direction to a method for the treatment of septic shock.
摘要翻译：本发明涉及一种用于预防或治疗由生物反应调节剂引起的一氧化氮产生引起的全身性低血压的有害生理作用的动物的方法。这种生物反应调节剂的实例包括但不限于细胞因子和内毒素。本发明也是治疗败血性休克的方法。

35. 发明授权

US5674836A Treatment of septic shock with iron-containing hemoprotein 失效
标题翻译：用含铁血红蛋白治疗败血性休克
公开(公告)号：US5674836A
公开(公告)日：1997-10-07
申请号：US184255
申请日：1994-01-18
申请人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
发明人： Robert G. Kilbourn , Joseph De Angelo , Joseph Bonaventura
IPC分类号： A61K38/16 , A61K38/42 , A61P9/00 , A61P9/12
CPC分类号： A61K38/42
摘要： The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also directed to a method for the treatment of septic shock.
摘要翻译：本发明涉及一种用于预防或治疗由生物反应调节剂引起的一氧化氮产生引起的全身性低血压的有害生理作用的动物的方法。这种生物反应调节剂的实例包括但不限于细胞因子和内毒素。本发明还涉及一种治疗败血性休克的方法。

36. 发明授权

US5612310A Methods for improving therapeutic effectiveness of agents for the treatment of solid tumors and other disorders 失效
标题翻译：提高治疗实体瘤和其他疾病的药物治疗效果的方法
公开(公告)号：US5612310A
公开(公告)日：1997-03-18
申请号：US66756
申请日：1993-05-24
申请人： Mark W. Dewhirst , Robert E. Meyer , Joseph Bonaventura , Joseph DeAngelo
发明人： Mark W. Dewhirst , Robert E. Meyer , Joseph Bonaventura , Joseph DeAngelo
IPC分类号： A61K31/00 , A61K31/195 , A61K31/198 , A61K31/4045 , A61K38/42 , A61K41/00 , A61K38/16
CPC分类号： A61K41/0052 , A61K31/00 , A61K31/195 , A61K31/198 , A61K31/4045 , A61K38/42 , Y10S514/832 , Y10S514/833
摘要： The present invention is directed to administration of a nitric oxide scavenger or a nitric oxide synthase inhibitor to enhance the effectiveness of tumor therapy with hypoxic or acidic chemotherapeutic agents or hyperthermia. In a specific example, administration of cell free hemoglobin, a nitric oxide scavenger, in conjunction with mitomycin C, a hypoxic cytotoxin, results in a significant delay in tumor growth of a human tumor xenograft in a mouse compared to mitomycin C alone.
摘要翻译：本发明涉及一氧化氮清除剂或一氧化氮合酶抑制剂的施用以增强用缺氧或酸性化学治疗剂或高热治疗肿瘤治疗的有效性。在具体实例中，与丝裂霉素C单独相比，将无细胞血红蛋白（一氧化氮清除剂）与丝裂霉素C（缺氧细胞毒素）联合导致小鼠中人肿瘤异种移植物的肿瘤生长显着延迟。

37. 发明授权

US4427416A Processes for extracting oxygen from fluids using immobilized hemoglobin 失效
标题翻译：使用固定化血红蛋白从流体中提取氧气的方法
公开(公告)号：US4427416A
公开(公告)日：1984-01-24
申请号：US372338
申请日：1982-04-27
申请人： Joseph Bonaventura , Celia Bonaventura
发明人： Joseph Bonaventura , Celia Bonaventura
IPC分类号： A61K38/00 , C01B13/02 , C07K14/805 , C01B13/00
CPC分类号： C01B13/0285 , C01B13/0262 , C07K14/805 , A61K38/00 , C01B2210/0046 , C01B2210/0062
摘要： An oxygen carrier, capable of reversibly binding and releasing oxygen, immobilized in a polymer matrix and a method of recovering dissolved oxygen from fluids utilizing the same.
摘要翻译：固定在聚合物基质中的能够可逆地结合和释放氧的氧载体，以及利用该载体从溶液中回收溶解氧的方法。

38. 发明授权

US4343715A Immobilized hemoglobin, and processes for extracting oxygen from fluids using the same 失效
标题翻译：固定化血红蛋白，以及使用其从流体中提取氧气的方法
公开(公告)号：US4343715A
公开(公告)日：1982-08-10
申请号：US196036
申请日：1980-10-10
申请人： Joseph Bonaventura , Celia Bonaventura
发明人： Joseph Bonaventura , Celia Bonaventura
IPC分类号： A61K38/00 , B01J20/28 , C01B13/02 , C07K14/805 , C01B13/00 , A61M16/00
CPC分类号： B01J20/28026 , B01J20/28004 , B01J20/28016 , B01J20/28045 , B01J20/28047 , C01B13/0262 , C01B13/0285 , C07K14/805 , A61K38/00 , C01B2210/0046 , C01B2210/0062
摘要： An oxygen carrier, capable of reversibly binding and releasing oxygen, immobilized in a polymer matrix and a method of recovering dissolved oxygen from fluids utilizing the same.
摘要翻译：固定在聚合物基质中的能够可逆地结合和释放氧的氧载体，以及利用该载体从溶液中回收溶解氧的方法。

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